4JN9: Crystal structure of the DepH

Citation:
Abstract
The disulfide bond is unusual in natural products and critical for thermal stability, cell permeability and bioactivity. DepH from Chromobacterium violaceum No. 968 is an FAD-dependent enzyme responsible for catalyzing the disulfide bond formation of FK228, an anticancer prodrug approved for the treatment of cutaneous T-cell lymphoma. Here we report the crystal structures of DepH and DepH complexed with a substrate analogue S,S'-dimethyl FK228 at 1.82 A and 2.00 A, respectively. Structural and biochemical analyses revealed that DepH, in contrast to the well characterized low molecular weight thioredoxin reductases (LMW TrxRs), is an NADP(+)-independent dithiol oxidase. DepH not only lacks a conserved GGGDXAXE motif necessary for NADP(+) binding in the canonical LMW TrxRs, but also contains a 11-residue sequence which physically impedes the binding of NADP(+). These observations explain the difference between NADP(+)-independent small molecule dithiol oxidases and NADP(+)-dependent thioredoxin reductases and provide insights for understanding the catalytic mechanism of dithiol oxidases involved in natural product biosynthesis.
PDB ID: 4JN9Download
MMDB ID: 118989
PDB Deposition Date: 2013/3/14
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Similar Structures:
Biological Unit for 4JN9: dimeric; determined by author and by software (PISA)
Molecular Components in 4JN9
Label Count Molecule
Proteins (2 molecules)
2
Deph
Molecule annotation
Chemicals (11 molecules)
1
2
2
2
3
1
4
1
5
5
* Click molecule labels to explore molecular sequence information.

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